Quantitative electroencephalogram (qEEG) monitors are often used to estimate depth of anesthesia and intraoperative recall during general anesthesia. As with any monitor, the processed numerical ...output is often misleading and has to be interpreted within a clinical context. For the safe clinical use of these monitors, a clear mental picture of the expected raw electroencephalogram (EEG) patterns, as well as a knowledge of the common EEG artifacts, is absolutely necessary. This has provided the motivation to write this tutorial. We describe, and give examples of, the typical EEG features of adequate general anesthesia, effects of noxious stimulation, and adjunctive drugs. Artifacts are commonly encountered and may be classified as arising from outside the head, from the head but outside the brain (commonly frontal electromyogram), or from within the brain (atypical or pathologic). We include real examples of clinical problem-solving processes. In particular, it is important to realize that an artifactually high qEEG index is relatively common and may result in dangerous anesthetic drug overdose. The anesthesiologist must be certain that the qEEG number is consistent with the apparent state of the patient, the doses of various anesthetic drugs, and the degree of surgical stimulation, and that the qEEG number is consistent with the appearance of the raw EEG signal. Any discrepancy must be a stimulus for the immediate critical examination of the patient's state using all the available information rather than reactive therapy to "treat" a number.
The true incidence of seizures caused by general anesthetic drugs is unknown. Abnormal movements are common during induction of anesthesia, but they may not be indicative of true seizures. ...Conversely, epileptiform electrocortical activity is commonly induced by enflurane, etomidate, sevoflurane and, to a lesser extent, propofol, but it rarely progresses to generalized tonic-clonic seizures. Even "nonconvulsant" anesthetic drugs occasionally cause seizures in subjects with preexisting epilepsy. These seizures most commonly occur during induction or emergence from anesthesia, when the anesthetic drug concentration is relatively low. There is no unifying neural mechanism of anesthetic drug-related seizurogenesis. However, there is a growing body of experimental work suggesting that seizures are not caused simply by "too much excitation," but rather by excitation applied to a mass of neurons which are primed to react to the excitation by going into an oscillatory seizure state. Increased gamma-amino-butyric acid (GABA)ergic inhibition can sensitize the cortex so that only a small amount of excitation is required to cause seizures. This has been postulated to occur 1) at the network level by increasing the propensity for reverberation (e.g., by prolongation of the "inhibitory lag"), or 2) via different effects on subpopulations of interneurons ("inhibiting-the-inhibitors") or 3) at the synaptic level by changing the chloride reversal potential ("excitatory GABA"). On the basis of applied neuropharmacology, prevention of anesthetic-drug related seizures would include 1) avoiding sevoflurane and etomidate, 2) considering prophylaxis with adjunctive benzodiazepines (alpha-subunit GABA(A) agonists), or drugs that impair calcium entry into neurons, and 3) using electroencephalogram monitoring to detect early signs of cortical instability and epileptiform activity. Seizures may falsely elevate electroencephalogram indices of depth of anesthesia.
This article is part of an American Board of Pediatrics Foundation-sponsored effort to analyze and forecast the pediatric subspecialty workforce between 2020 and 2040. Herein, an overview of the ...current pediatric gastroenterology workforce is provided, including demographics, work characteristics, and geographic distribution of practitioners. Brief context is provided on the changing nature of current practice models and the increasing prevalence of some commonly seen disorders. On the basis of a rigorous microsimulation workforce projection model, projected changes from 2020 to 2040 in the number of pediatric gastroenterologists and clinical workforce equivalents in the United States are presented. The article closes with a brief discussion of training, clinical practice, policy, and future workforce research implications of the data presented. This data-driven analysis suggests that the field of pediatric gastroenterology will continue to grow in scope and complexity, propelled by scientific advances and the increasing prevalence of many disorders relevant to the discipline. The workforce is projected to double by 2040, a growth rate faster than most other pediatric subspecialties. Disparities in care related to geography, race, and ethnicity are among the most significant challenges for the years ahead. Changes to training and education, incentives to meet the needs of underserved populations, and new multidisciplinary models for health care delivery will be necessary to optimally meet the volume, diversity, and complexity of children with gastroenterological diseases in the years ahead.
Malleable MPP and inflatable IPP penile prosthesis surgery for the management of erectile dysfunction is a reliable treatment option with high success rates and excellent patient satisfaction; ...however, Medicaid coverage transparency is poor leaving a knowledge gap in this population.
The present study seeks to assess Medicaid coverage for MPP and IPP by state as evidenced by inclusion in publicly available physician fee schedules.
State Medicaid websites were utilized to access public physician fee schedules. Individual search queries were performed for CPT codes 54400 and 54405 which represent insertion of MPP and IPP, respectively. Data were recorded for each device, including the coverage status, physician fees, and the presence of clear documentation of a prior authorization requirement.
Medicaid physician fee schedules were accessible for 49 out of 50 US states, and 28 states reported coverage for at least one type of penile prosthesis.
Two states reported coverage for MPP only, one state reported coverage for IPP only, and 24 states reported coverage for both devices. One state reported that it did not cover either device, but listed coverage for a self-contained IPP (CPT 54401) only. Mean physician reimbursement was $477.15 (290.82–$1175.50) for MPP placement and $691.76 (421.68–$1794.27) for IPP. Eleven states documented prior authorization requirements within their fee schedules, while the remaining 17 states did not. Criteria for approval for prior authorization were not clearly stated in any fee schedule.
Efforts to clearly document approval criteria and educate Men's Health providers on available coverage could result in a significant improvement in sexual satisfaction in the Medicaid population.
Graphical representation of states offering Medicaid penile prosthetic coverage and physician reimbursement ranges are provided with comparison to Medicare rates. Limitations include heterogeneity in fee schedules, lack of prior authorization requirement details, inability to correlate to successful claims data, and the evolving nature of Medicaid coverage for the given procedures.
Medicaid coverage exists for penile prosthetic surgery in 28 states, although often with significant, non-transparent prior authorization criteria.
Barnard JT, Grimaud L, Yafi FA. Does Medicaid Cover Penile Prosthesis Surgery? A State-by-State Analysis. J Sex Med 2021;18:1455–1460.
The apolipoprotein E (APOE) ε4 allele is the major genetic risk factor for Alzheimer's disease (AD). Multiple regulatory elements, spanning the extended TOMM40-APOE-APOC2 region, regulate gene ...expression at this locus. Regulatory element DNA methylation changes occur under different environmental conditions, such as disease. Our group and others have described an APOE CpG island as hypomethylated in AD, compared to cognitively normal controls. However, little is known about methylation of the larger TOMM40-APOE-APOC2 region. The hypothesis of this investigation was that regulatory element methylation levels of the larger TOMM40-APOE-APOC2 region are associated with AD. The aim was to determine whether DNA methylation of the TOMM40-APOE-APOC2 region differs in AD compared to cognitively normal controls in post-mortem brain and peripheral blood. DNA was extracted from human brain (n = 12) and peripheral blood (n = 67). A methylation array was used for this analysis. Percent methylation within the TOMM40-APOE-APOC2 region was evaluated for differences according to tissue type, disease state, AD-related biomarkers, and gene expression. Results from this exploratory analysis suggest that regulatory element methylation levels within the larger TOMM40-APOE-APOC2 gene region correlate with AD-related biomarkers and TOMM40 or APOE gene expression in AD.
Substitutions at residue Y181 in HIV-1 reverse transcriptase (RT), in particular, Y181C, Y181I, and Y181V, are associated with nonnucleoside RT inhibitor (NNRTI) cross-resistance. In this study, we ...used kinetic and thermodynamic approaches, in addition to molecular modeling, to gain insight into the mechanisms by which these substitutions confer resistance to nevirapine (NVP), efavirenz (EFV), and rilpivirine (RPV). Using pre-steady-state kinetics, we found that the dissociation constant (
) values for inhibitor binding to the Y181C and Y181I RT-template/primer (T/P) complexes were significantly reduced. In the presence of saturating concentrations of inhibitor, the Y181C RT-T/P complex incorporated the next correct deoxynucleoside triphosphate (dNTP) more efficiently than the wild-type (WT) complex, and this phenotype correlated with decreased mobility of the RT on the T/P substrate. Interestingly, we found that the Y181F substitution in RT-which represents a transitional mutation between Y181 and Y181I/V, or a partial revertant-conferred hypersusceptibility to EFV and RPV at both the virus and enzyme levels. EFV and RPV bound more tightly to Y181F RT-T/P. Furthermore, inhibitor-bound Y181F RT-T/P was less efficient than the WT complex in incorporating the next correct dNTP, and this could be attributed to increased mobility of Y181F RT on the T/P substrate. Collectively, our data highlight the key role that Y181 in RT plays in NNRTI binding.
Dried droplets from a series of 1wt% lysozyme solutions with increasing amounts of added NaCl; (a) 0.00, (b) 0.01, (c) 0.10, (d) 0.50, and (e) 1.00wt% NaCl. The pattern in (f) is from a drop ...containing only 1.00wt% NaCl for comparison. Display omitted
► We study pattern formation during evaporation of aqueous lysozyme and NaCl solution droplets. ► The effect of NaCl content is examined by varying the solution concentration of NaCl. ► Morphological evolution of droplet evaporation is visualized with time-lapse video. ► Deposits exhibit an amorphous peripheral ring and interior regions containing crystallites and dendritic forms. ► Patterns are dependent on NaCl concentration.
Solute self-organization during evaporation of colloidal sessile droplets has attracted the attention of researchers over the past few decades due to a variety of technological applications. Recently, pattern formation during evaporation of various biofluids has been studied due to potential applications in screening and diagnosis. The complex morphological patterns in the deposit are unique to various disorders and are influenced by various physical mechanisms occurring during evaporation. These complex patterns can be better understood by studying evaporation of model solutions of biological relevance. Here, we examine the general features of pattern formation during sessile droplet evaporation of aqueous lysozyme solutions with varying concentrations of NaCl. Lysozyme is a globular protein found in biological fluids such as tears and saliva. The morphological evolution of the droplet is studied by time-lapse video during evaporation via reflection optical microscopy. The final deposits exhibit an amorphous peripheral ring and interior regions containing crystallites and dendritic forms, dependent on NaCl concentration. Scanning electron microscopy (SEM) images demonstrate the multi-scale hierarchical nature of these structures.
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